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Heal thyself: Systems biology model reveals how cells avoid becoming cancerous

wal analyzed the effect of exposure of yeast cells to MMS (methyl-methanesulfonate), a chemical known to cause DNA damage in a manner similar to that of certain mutagens in tobacco smoke. The alkylation injury caused by MMS results in small kinks in the otherwise smoothly curving double helix of DNA. Cells rapidly identify the damage, stop dividing, excise the damaged DNA, and use several alternate methods to substitute a clean copy of genetic material.

"It's almost as if cells have something akin to a computer program that becomes activated by DNA damage, and that program enables the cells to respond very quickly," said Mak. "And this program is easily recognizable as operating in everything from yeasts to humans and mice to fruit flies."

Researchers have previously identified hundreds of genes involved in repairing MMS damage. However, they have been mystified by another group of genes whose expression is sharply affected by DNA damage, but which appear to play no role in repairing the damage itself.

Ideker's team uncovered a tangled network of interactions of 30 transcription factors with more than 5,000 yeast genes. A transcription factor is a protein that, either alone or in combination with other transcription factors, binds to one or more genes to affect the expression of that gene or genes. The discovery by Ideker's group of a huge network of transcription factor-gene interactions was made possible by new biotechnology tools that provide comprehensive analysis of cells, like a passerby suddenly being able to monitor all the telephone calls made within a city.

The team discovered that part of the interaction network was involved, as expected, in repairing damaged DNA. However, they were surprised to find that a much larger part of the network is involved in modulating the expression of genes not directly related to DNA repair, such as genes involved in cell growth and division, protein degradation, responses to stress, and other metabolic
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Contact: Rex Graham
ragraham@ucsd.edu
858-822-3075
University of California - San Diego
18-May-2006


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